The proposed studies are designed to improve our understanding of how biomimetic approaches can be used to remineralize carious enamel and properly restore normal tooth enamel structure and properties. Our working hypothesis is that the restoration or regeneration of proper tooth structure and function can be achieved through the regulation of mineral ion diffusion, crystal growth kinetics and crystal orientation. Studies will be guided by a working mathematical model that will be developed to describe the dynamics and interrelationships of these key events, based on experimental data generated using a novel chemical approach to remineralize in vivo-like incipient carious lesions. Using this model as a basis, novel biomimetic approaches to remineralize and regenerate tooth structures will be studied. The proposed biomimetic strategies are based on our current state of knowledge of how mineral deposition and organization are regulated in developing mineralized tissues. Given the high prevalence of dental caries, there is a tremendous need for restorative procedures that are superior to those presently available. The long-term goal of these studies is to develop new procedures to regenerate normal tooth structure and function. In general, these studies consider the importance of ion diffusion and driving forces for dissolution and precipitation in human enamel, along with the role of synthetic and biologically relevant molecules that regulate the rate and shape of growing enamel mineral crystals. Specifically, we propose: 1. To determine the mechanism and potential effectiveness of novel acidic remineralizing solutions in vitro; 2. To determine the mechanism and remineralization effectiveness of supersaturated calcium phosphate solutions that are stabilized by selected salivary proteins and peptides; 3.To determine the remineralization effectiveness of novel supersaturated calcium phosphate solutions that are stabilized by pyrophosphate, where remineralization kinetics are regulated by added phosphatases; 4.To develop an in vitro system to study the remineralization of enamel fissure lesions using microradiography, polarized light microscopy and X-ray microtomography; and 5. To determine the possible role of stabilized amorphous calcium phosphate (ACP) as a precursor for the epitaxial growth of mature enamel crystals, with particular attention on the remineralization and regeneration of carious enamel fissure tissue.